Increased caffeine intake is linked to a decreased risk of Parkinson’s disease (PD) in people who have a LRRK2 genetic mutation, which is associated with the disease. These are the results of a recent MJFF-supported study, published in the journal Neurology, and led by Grace Crotty, MD, a recent graduate of The Michael J. Fox Foundation’s Edmond J. Safra Fellowship in Movement Disorders, Instructor in Neurology at Harvard Medical School and Assistant in Neurology at Massachusetts General Hospital in Boston. While prior research has demonstrated an association between caffeine and PD, this study is one of the first to show possible benefits of caffeine in people with a genetic risk for Parkinson’s. Understanding how environmental factors, such as caffeine intake, interact with genetic factors to push toward or protect from PD helps researchers learn more about disease mechanisms, individual courses (why one person gets disease and another doesn’t), and potential treatments. For more about the study, its results, and what they mean for people with Parkinson’s or at risk for the disease, we spoke with Dr. Crotty.
The Michael J. Fox Foundation for Parkinson’s Research (MJFF): Let’s start with the big picture. Why study caffeine and Parkinson’s?
Grace Crotty (GC): There is a body of well-established literature on caffeine and Parkinson’s disease, mainly studying people at the population level or through dietary questionnaires, showing that caffeine drinkers have a lower risk of developing PD. We wanted to look at caffeine and its metabolites (the breakdown products of caffeine in the body) to see if these differed not only in people with non-genetic Parkinson’s, but also in people who developed PD with a LRRK2 genetic mutation, which increases risk for the disease. We thought caffeine-related metabolites would be lower in people with PD because of previous research, but we didn’t know if it would be lower among LRRK2 mutation carriers.
MJFF: Why look at caffeine in people with LRRK2?
GC: LRRK2 genetic mutations are a major risk factor for PD. But they have incomplete penetrance, meaning that not everyone carrying this mutation develops the disease. This suggests that there are other genetic or environmental factors (such as caffeine intake) that modify risk. It’s of great interest to the research community to identify these modifiers, which could pave the way to preventative trials, or studies looking at therapies to prevent disease.
MJFF: How did you conduct the study?
GC: We looked at 368 participants in MJFF’s LRRK2 Cohort Consortium, a rich database that includes information from control volunteers and people with Parkinson’s, both with and without the LRRK2 mutation. On each person’s blood sample, we performed metabolomic profiling, which examines caffeine, carbohydrates, lipids, urate, and other compounds. We compared metabolites between people with Parkinson’s and controls and also made these comparisons among those with and without a LRRK2 mutation. A subset of people also completed a questionnaire about their dietary intake of caffeine-containing drinks, including coffee, tea and soda.
MJFF: What did you find?
GC: Across all metabolites, the most significant difference was in caffeine and related analytes. Caffeine levels were lower in people with Parkinson’s versus controls, which is consistent with what’s documented in previous literature. We were surprised to find, though, that the greatest difference in caffeine levels was between people with a LRRK2 mutation. People with a LRRK2 mutation and PD had a 76 percent lower caffeine concentration in the blood than people with LRRK2 without PD. Supporting this data, questionnaires showed that among people with a LRRK2 mutation, those with PD reported taking in 41 percent less caffeine per day than those without Parkinson’s. One might ask whether people at greater risk for PD avoid caffeine and that’s why we see an association between increased caffeine and decreased Parkinson’s. A lower dietary intake may be part of the explanation, but interestingly, when we adjusted for dietary intake, we still saw a difference in metabolites. So there may be a difference in caffeine absorption or metabolism between people with and without PD.
MJFF: What do these results mean?
GC: It’s exciting to see this intriguing association between caffeine and PD resistance in people who are at increased risk due to LRRK2 mutations. But it’s worth stressing that it’s an association, not proof that caffeine is a cause of reduced penetrance. Further research is necessary, and my colleagues and I plan to see if these results replicate in another genetic cohort in the near future. Ultimately, this could lead us to new ways, involving caffeine pathways, to treat or even prevent Parkinson’s.
MJFF: Should people add caffeine to their diet to prevent Parkinson’s?
GC: While we would not recommend anyone significantly change their lifestyle based on this study, these results add to the growing body of evidence in support of caffeine. Coffee and tea, for example, typically are well-tolerated and low-risk, and contain antioxidants that may benefit overall health. If you enjoy caffeine, drinking it in moderation may have positive effects. But always talk with your doctor or dietitian about what’s best for you and your symptoms.